DESCRIPTION: Cyclodextrins (CDs) are well-known host molecules which are used for complexation and reaction catalysis. Their properties (well-defined cavities, small sizes, ease of functionalization) make them ideal enzyme models. Several interesting enzyme-like macromolecules have been synthesized by attaching catalytic groups to CDs. These supramolecular hosts have two features basic to enzymes: a binding site and a catalytic ensemble. One feature they lack is an environmental switch, that is, some cue which tells the enzyme when to function and when to remain dormant. This proposal is aimed at building a switch into Beta-CD derivatives with the goal of understanding the biological mechanism for enzyme activation at the molecular level. The environmental cue will be hydrogen ion concentration, perhaps the most fundamental of all cues. The switching mechanism will be pH-indicator dye molecules which have been covalently bonded at two sites (capped) on Beta-CD. The thesis of this proposal is that such a supramolecular system will exhibit pH dependent binding. In the extreme case, they would be strongly binding in one pH range, while essentially non binding outside this range. The host-guest structures for both strongly-binding and weakly-binding forms will be elucidated through NMR, and their thermodynamic characteristics will be determined through uv/vis spectrophotometry. Switchable CDs may be useful in pharmacology as selective drug-delivery materials.